Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT01990560
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether mifepristone is an effective treatment for hyperglycemia due to mild hypercortisolism.

• To test the hypothesis that GR blockade with mifepristone will decrease the severity of metabolic syndrome features as measured by waist circumference, lipid profile, body mass index, blood pressure and insulin resistance, measured by HOMA-IR score.

• To test the hypothesis that GR blockade with mifepristone will improve QoL, depression and anxiety scores, measured by validated assessments, in patients with mild hypercortisolism.

Condition or Disease	Intervention/Treatment	Phase
Mild Hypercortisolism	Drug: Mifepristone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mifepristone Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response	Drug: Mifepristone; All patients in the study will receive daily Mifepristone for 6 months and primary and secondary outcomes will be assessed before and after the 6 month treatment period; Other Names: Korlym

Outcome Measures

Primary Outcome Measures

1. A1C Level [Baseline, 3 months, and 6 months]

   Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin

2. HOMA-IR [Baseline and 6 months]

   Change in hyperglycemia assessed by Homeostatic Model Assessment of Insulin Resistance, HOMA-IR (a validated assessment of insulin resistance). HOMA-IR = fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.

Secondary Outcome Measures

1. Waist Circumference [Baseline and 6 months]

   Change in metabolic syndrome as assessed by waist circumference

2. Body Mass Index (BMI) [Baseline and 6 months]

   Change in metabolic syndrome as assessed by BMI

3. Fasting Lipid Profile [Baseline and 6 months]

   Change in metabolic syndrome as assessed by fasting lipid profile which includes Low-density lipoproteins ( LDL), High-density lipoproteins (HDL), and Triglycerides (Trigs) levels, and total cholesterol which is the sum of HDL plus LDL and 20% of trigs.

4. Weight [Baseline and 6 months]

   Change in metabolic syndrome as assessed by weight

5. CushingQoL [Baseline and 6 months]

   Change in Quality of Life - as assessed by the Cushing's Quality of Life questionnaire (CushingQoL). Patient completed questionnaire, 12 items, each scored on a 5 point score, resulting in a score of 12 (worst) to 60 (best) where higher scores indicate more favorable QOL.

6. Nottingham Health Profile (NHP) [Baseline and 6 months]

   Change in Quality of Life as assessed by the Nottingham Health Profile (NHP) which is a patient reported questionnaire to measure a patient's view of their own health status. There are 6 sections (Energy level, Pain, Emotional Reaction, Sleep, Social Isolation, and Physical Abilities. All questions have only yes/no answer options and each section score is weighted so that the possible score range for any section is 0-100. The higher the score, the greater the number and severity of problems.

7. Hospital Anxiety and Depression Scale (HADS) [Baseline and 6 months]

   Change in Quality of Life as assessed by the Hospital Anxiety and Depression Scale (HADS). Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression

8. Quality of Life [Baseline and 6 months]

   Change in Quality of Life as assessed by the Beck Depression Inventory. a 21-question multiple choice, self-report inventory that is used for measuring the severity of anxiety. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe anxiety symptoms.

9. State Trait Anxiety Inventory (STAI) [Baseline and 6 months]

   Change in Quality of Life - as assessed by the State Trait Anxiety Inventory (STAI). The State-Trait Anxiety Inventory both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored and averaged. Total scores range from 20 to 80, with higher scores correlating with greater anxiety.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age

• Incidentally noted adrenal nodule <4 cm with benign imaging characteristics

• Evidence of mild hypercortisolism

• Evidence of diabetes or abnormal glucose tolerance

Exclusion Criteria:

• contraindication to mifepristone

• Indication for unilateral adrenalectomy

• Evidence of other adrenal hormone hypersecretion

• lactating mothers

• women of childbearing age unwilling to use an effective, nonhormonal form of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Alice C Levine, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

• Debono M, Chadarevian R, Eastell R, Ross RJ, Newell-Price J. Mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol: a pilot study. PLoS One. 2013;8(4):e60984. doi: 10.1371/journal.pone.0060984. Epub 2013 Apr 5.
• Feelders RA, Hofland LJ. Medical treatment of Cushing's disease. J Clin Endocrinol Metab. 2013 Feb;98(2):425-38. doi: 10.1210/jc.2012-3126. Epub 2013 Jan 23. Review.
• Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48.
• Garrapa GG, Pantanetti P, Arnaldi G, Mantero F, Faloia E. Body composition and metabolic features in women with adrenal incidentaloma or Cushing's syndrome. J Clin Endocrinol Metab. 2001 Nov;86(11):5301-6.
• Lambert JK, Goldberg L, Fayngold S, Kostadinov J, Post KD, Geer EB. Predictors of mortality and long-term outcomes in treated Cushing's disease: a study of 346 patients. J Clin Endocrinol Metab. 2013 Mar;98(3):1022-30. doi: 10.1210/jc.2012-2893. Epub 2013 Feb 7.
• Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004 Apr;25(2):309-40. Review.
• Neary NM, Booker OJ, Abel BS, Matta JR, Muldoon N, Sinaii N, Pettigrew RI, Nieman LK, Gharib AM. Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab. 2013 May;98(5):2045-52. doi: 10.1210/jc.2012-3754. Epub 2013 Apr 4.
• Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125. Epub 2008 Mar 11.
• Parker BA, Sturm K, MacIntosh CG, Feinle C, Horowitz M, Chapman IM. Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects. Eur J Clin Nutr. 2004 Feb;58(2):212-8.
• Tauchmanovà L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Palmieri EA, Fazio S, Lombardi G. Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab. 2002 Nov;87(11):4872-8.
• Terzolo M, Pia A, Alì A, Osella G, Reimondo G, Bovio S, Daffara F, Procopio M, Paccotti P, Borretta G, Angeli A. Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab. 2002 Mar;87(3):998-1003.
• Young WF Jr. Management approaches to adrenal incidentalomas. A view from Rochester, Minnesota. Endocrinol Metab Clin North Am. 2000 Mar;29(1):159-85, x. Review.

• Responsible Party: Alice C. Levine, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01990560
• Other Study ID Numbers: GCO 13-1061
• First Posted: Nov 21, 2013
• Last Update Posted: Mar 2, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Alice C. Levine, Professor, Icahn School of Medicine at Mount Sinai: mild hypercortisolism; Subclinical Cushing's Syndrome; Preclinical Cushing's Syndrome
• Additional relevant MeSH terms: Cushing Syndrome; Adrenocortical Hyperfunction; Mifepristone

Study Results

Participant Flow

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (10.6)
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%

Outcome Measures

1. Primary Outcome

Title	A1C Level
Description	Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin
Time Frame	Baseline, 3 months, and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	8
Baseline	6.2 (0.58)
3 months	6.1375 (0.49)
6 months	6.125 (0.72)

2. Primary Outcome

Title	HOMA-IR
Description	Change in hyperglycemia assessed by Homeostatic Model Assessment of Insulin Resistance, HOMA-IR (a validated assessment of insulin resistance). HOMA-IR = fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant on insulin. another participant had data missing at 6 months.

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	6
Baseline	2.418 (1.64)
6 months	1.465 (1.19)

3. Secondary Outcome

Title	Waist Circumference
Description	Change in metabolic syndrome as assessed by waist circumference
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	8
Baseline	103.25 (17.43)
6 months	99.3125 (101.25)

4. Secondary Outcome

Title	Body Mass Index (BMI)
Description	Change in metabolic syndrome as assessed by BMI
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	8
Baseline	35.1538 (15.02)
6 months	34.5463 (15.84)

5. Secondary Outcome

Title	Fasting Lipid Profile
Description	Change in metabolic syndrome as assessed by fasting lipid profile which includes Low-density lipoproteins ( LDL), High-density lipoproteins (HDL), and Triglycerides (Trigs) levels, and total cholesterol which is the sum of HDL plus LDL and 20% of trigs.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant data missing at 6 month

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	8
Total Cholesterol Baseline	178.63 (31.35)
Total Cholesterol 6 months	171.43 (54.62)
LDL baseline	97.88 (22.34)
LDL 6 months	104.37 (44.69)
HDL Baseline	59.13 (19.50)
HDL 6 months	46.86 (14.26)
Trigs Baseline	107.88 (43.90)
Trigs 6 months	100.29 (20.21)

6. Secondary Outcome

Title	Weight
Description	Change in metabolic syndrome as assessed by weight
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant had data missing at 6 months

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	8
Baseline	99.57 (38.68)
6 months	97.75 (41.15)

7. Secondary Outcome

Title	CushingQoL
Description	Change in Quality of Life - as assessed by the Cushing's Quality of Life questionnaire (CushingQoL). Patient completed questionnaire, 12 items, each scored on a 5 point score, resulting in a score of 12 (worst) to 60 (best) where higher scores indicate more favorable QOL.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	7
Baseline	37.2857 (9.86)
6 months	38.7857 (10.20)

8. Secondary Outcome

Title	Nottingham Health Profile (NHP)
Description	Change in Quality of Life as assessed by the Nottingham Health Profile (NHP) which is a patient reported questionnaire to measure a patient's view of their own health status. There are 6 sections (Energy level, Pain, Emotional Reaction, Sleep, Social Isolation, and Physical Abilities. All questions have only yes/no answer options and each section score is weighted so that the possible score range for any section is 0-100. The higher the score, the greater the number and severity of problems.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	7
Energy Level (EL) Baseline	32.60
EL 6 months	45.40
Pain (P) Baseline	24.88
P 6 months	32.08
Emotional Reaction (ER) Baseline	27.03
ER 6 months	35.09
Sleep (S) Baseline	24.87
S 6 months	31.15
Social Isolation (SI) Baseline	20.09
SI 6 months	31.15
Physical Abilities (PA) Baseline	23.06
PA 6 months	27.49

9. Secondary Outcome

Title	Hospital Anxiety and Depression Scale (HADS)
Description	Change in Quality of Life as assessed by the Hospital Anxiety and Depression Scale (HADS). Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	7
Baseline	16.2857 (10.90)
6 months	11.1667 (8.23)

10. Secondary Outcome

Title	Quality of Life
Description	Change in Quality of Life as assessed by the Beck Depression Inventory. a 21-question multiple choice, self-report inventory that is used for measuring the severity of anxiety. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe anxiety symptoms.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	7
Baseline	16.1429 (10.32)
6 months	11.7143 (11.70)

11. Secondary Outcome

Title	State Trait Anxiety Inventory (STAI)
Description	Change in Quality of Life - as assessed by the State Trait Anxiety Inventory (STAI). The State-Trait Anxiety Inventory both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored and averaged. Total scores range from 20 to 80, with higher scores correlating with greater anxiety.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Measure Participants	7
Baseline	25.4286 (17.61)
6 months	28.8571 (10.92)

Adverse Events

Arm/Group Title	Mifepristone
Arm/Group Description	Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
All Cause Mortality
	Mifepristone
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Metabolism and nutrition disorders
Hypokalemia	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Drug Rash	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.